Araştırma Makalesi
KLF4, SHH ve Hif1a Susturulmasının Malign Melanom Kanser Kök Hücrelerinde miRNA Ekspresyonuna Etkisi
Öz
Amaç: mikroRNA'lar (miRNA'lar) gen regülasyonunda önemli bir rol oynar ve farklılaşma, proliferasyon ve apoptoz gibi çeşitli hücresel süreçleri etkiler. Bu çalışmada, malign melanom kök hücrelerinde (CSC'ler) ve kök hücre olmayan hücrelerde (NSC'ler) üç spesifik miRNA'nın (Hsa-miR-21-5p, Hsa-miR-9-5p ve Hsa-miR-200a-5p) ekspresyonu araştırılmıştır.
Yöntem: Malign melanoma hücre hattı olan CHL-1 hücrelerinden CSC ve NCSC hücreleri CD133 belirteci baz alınarak elde edilmiştir. CD133+ hücreler HIF1a, KLF4, ve SHH siRNA ile muamele edilerek üç farklı miRNA ekspresyon seviyesi gruplar arası karşılaştırılmıştır.
Bulgular: Bulgularımız Hsa-miR-200a-5p ekspresyonunun her iki hücre grubunda da benzer olduğunu ortaya koymuştur. Buna karşılık, Hsa-miR-21-5p ve Hsa-miR-9-5p, NCSC hücrelerinde önemli ölçüde yüksek ifade edilmiştir. Daha ileri analizler KLF4'ün susturulmasının bu miRNA'ların ifade düzeylerini önemli ölçüde etkilemediğini göstermiştir. Bununla birlikte, SHH'nin susturulması Hsa-miR-21-5p'nin önemli ölçüde düşük regülasyonu ve Hsa-miR-9-5p'nin önemli ölçüde yüksek ifadelenmesi ile sonuçlanmıştır. Ek olarak, Hif1a'nın susturulması hem Hsa-miR-21-5p hem de Hsa-miR-9-5p'nin aşağı regülasyonuna yol açmıştır.
Sonuç: Elde edilen bulgular, farklı hücresel bağlamlarda miRNA ifadesinin karmaşık düzenleyici mekanizmalarını vurgulamakta ve spesifik gen susturmaya yanıt olarak bu miRNA'lar için potansiyel roller önermektedir.
Anahtar Kelimeler
Proje Numarası
20785
Kaynakça
- Moran B, Silva R, Perry AS, Gallagher WM. Epigenetics of malignant melanoma. Semin Cancer Biol [Internet]. 2018;51:80–8. Available at: https://www.sciencedirect.com/science/article/pii/S1044579X1730130X
- Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D. Epidemiological trends in skin cancer. Dermatol Pract Concept [Internet]. 30 Nisan 2017;7(2):1–6. Available at: https://pubmed.ncbi.nlm.nih.gov/28515985
- Hessler M, Jalilian E, Xu Q, Reddy S, Horton L, Elkin K, vd. Melanoma biomarkers and their potential application for in vivo diagnostic imaging modalities. Int J Mol Sci. 2020;21(24):9583.
- Liu Z, Wang H, Sun C, He Y, Xia T, Wang J, vd. ZWZ-3, a Fluorescent Probe Targeting Mitochondria for Melanoma Imaging and Therapy [Internet]. C. 13, Frontiers in Pharmacology . 2022. Available at: https://www.frontiersin.org/article/10.3389/fphar.2022.829684
- Kuşoğlu A, Biray Avcı Ç. Cancer stem cells: A brief review of the current status. Gene [Internet]. 2019;681:80–5. Available at: https://www.sciencedirect.com/science/article/pii/S0378111918310163
- Jain P, Pillai M, Duddu AS, Somarelli JA, Goyal Y, Jolly MK. Dynamical hallmarks of cancer: Phenotypic switching in melanoma and epithelial-mesenchymal plasticity. Semin Cancer Biol [Internet]. 2023;96:48–63. Available at: https://www.sciencedirect.com/science/article/pii/S1044579X23001293
- Boudreault J, Wang N, Ghozlan M, Lebrun J-J. Transforming Growth Factor-β/Smad Signaling Inhibits Melanoma Cancer Stem Cell Self-Renewal, Tumor Formation and Metastasis. C. 16, Cancers. 2024.
- Wu J, Li W, Su J, Zheng J, Liang Y, Lin J, vd. Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells. Sci Rep [Internet]. 2024;14(1):12270. Available at: https://doi.org/10.1038/s41598-024-62913-3
- Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, vd. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther [Internet]. 2020;5(1):8. Available at: https://doi.org/10.1038/s41392-020-0110-5
- Bu P, Luo C, He Q, Yang P, Li X, Xu D. MicroRNA-9 inhibits the proliferation and migration of malignant melanoma cells via targeting sirituin 1. Exp Ther Med [Internet]. 2017/06/13. Ağustos 2017;14(2):931–8. Available at: https://pubmed.ncbi.nlm.nih.gov/28810544
- Bustos MA, Ono S, Marzese DM, Oyama T, Iida Y, Cheung G, vd. MiR-200a Regulates CDK4/6 Inhibitor Effect by Targeting CDK6 in Metastatic Melanoma. J Invest Dermatol [Internet]. 2017;137(9):1955–64. Available at: http://www.sciencedirect.com/science/article/pii/S0022202X17315282
- Liu S, Kumar SM, Lu H, Liu A, Yang R, Pushparajan A, vd. MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma. J Pathol. Ocak 2012;226(1):61–72.
- Melnik BC. MiR-21: an environmental driver of malignant melanoma? J Transl Med [Internet]. 27 Haziran 2015;13:202. Available at: https://pubmed.ncbi.nlm.nih.gov/26116372
- Satzger I, Mattern A, Kuettler U, Weinspach D, Niebuhr M, Kapp A, vd. microRNA-21 is upregulated in malignant melanoma and influences apoptosis of melanocytic cells. Exp Dermatol. Temmuz 2012;21(7):509–14.
- van Kempen LC, van den Hurk K, Lazar V, Michiels S, Winnepenninckx V, Stas M, vd. Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression. Virchows Arch. Ekim 2012;461(4):441–8.
- Gajos-Michniewicz A, Czyz M. Role of miRNAs in Melanoma Metastasis. Cancers (Basel). Mart 2019;11(3).
- Rhim J, Baek W, Seo Y, Kim JH. From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells. Eylül 2022;11(18).
- Yang CH, Yue J, Pfeffer SR, Handorf CR, Pfeffer LM. MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells. J Biol Chem. Kasım 2011;286(45):39172–8.
- Xu D, Chen X, He Q, Luo C. MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1. Onco Targets Ther. 2016;9:7047–57.
- Park S-M, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. Nisan 2008;22(7):894–907.
- Klicka K, Grzywa TM, Mielniczuk A, Klinke A, Włodarski PK. The role of miR-200 family in the regulation of hallmarks of cancer. Front Oncol [Internet]. 2022;12. Available at: https://www.frontiersin.org/articles/10.3389/fonc.2022.965231
- Chen W-Y, Xu Y-Y, Zhang X-Y. Targeting GOLM1 by microRNA-200a in melanoma suppresses cell proliferation, invasion and migration via regulating PI3K/Akt signaling pathway and epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci. Ağustos 2019;23(16):6997–7007.
- Botti G, Cerrone M, Scognamiglio G, Anniciello A, Ascierto PA, Cantile M. Microenvironment and tumor progression of melanoma: new therapeutic prospectives. J Immunotoxicol. 2013;10(3):235–52.
- Yue B. Biology of the extracellular matrix: an overview. J Glaucoma. 2014;23(8 Suppl 1):S20-3.
- Ozdil B, Biray Avci C, Calik-Kocaturk D, Gorgulu V, Uysal A, Guler G, vd. Modulating cancer stem cell characteristics in CD133+ melanoma cells through HIF1α, KLF4, and SHH silencing Berrin. unpublished. 2024.
- Ozdil Bay B. MALİGN MELANOMA KANSER KÖK HÜCRE MODELİNDE HİF1A GENİNİN SUSTURULMASI İLE İNCELENMESİ Doktora Tezi HİF1A GENİNİN SUSTURULMASI İLE. 2023.
- Gunel NS, Birden N, Kurt CC, Bagca BG, Shademan B, Sogutlu F, vd. Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer. Mol Biol Rep [Internet]. 2021;48(8):6085–91. Available at: https://doi.org/10.1007/s11033-021-06616-2
- Metsalu T, Vilo J. ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic Acids Res [Internet]. 01 Temmuz 2015;43(W1):W566–70. Available at: https://doi.org/10.1093/nar/gkv468
- Varrone F, Caputo E. The miRNAs Role in Melanoma and in Its Resistance to Therapy. C. 21, International Journal of Molecular Sciences. 2020.
- Poniewierska-Baran A, Zadroga Ł, Danilyan E, Małkowska P, Niedźwiedzka-Rystwej P, Pawlik A. MicroRNA as a Diagnostic Tool, Therapeutic Target and Potential Biomarker in Cutaneous Malignant Melanoma Detection-Narrative Review. Int J Mol Sci. Mart 2023;24(6).
- Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev cancer. 2006;6(4):259–69.
- Ghafouri-Fard S, Gholipour M, Taheri M. MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets. Front Oncol [Internet]. 2021;11. Available at: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.608987
- Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. Şubat 2008;21(1):39–55.
- Madjd Z, Erfani E, Gheytanchi E, Moradi-Lakeh M, Shariftabrizi A, Asadi-Lari M. Expression of CD133 Cancer Stem Cell Marker in Melanoma: A Systematic Review and Meta-Analysis. Int J Biol Markers [Internet]. 01 Nisan 2016;31(2):118–25. Available at: https://doi.org/10.5301/jbm.5000209
- He Z, He J, Xie K. KLF4 transcription factor in tumorigenesis. Cell Death Discov [Internet]. 2023;9(1):118. Available at: https://doi.org/10.1038/s41420-023-01416-y
- Luo X, Zhang Y, Meng Y, Ji M, Wang Y. Prognostic significance of KLF4 in solid tumours: an updated meta-analysis. BMC Cancer [Internet]. 2022;22(1):181. Available at: https://doi.org/10.1186/s12885-022-09198-9
- Chen B, Li L, Li M, Wang X. HIF1A expression correlates with increased tumor immune and stromal signatures and aggressive phenotypes in human cancers. Cell Oncol (Dordrecht, Netherlands). Ekim 2020;43(5):877–88.
- Xu L, Li K, Li J, Liu L, Xu F, Xu Y, vd. MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance. Oncol (Tech Sci Press. 2022;24(3).
- Yuva-Aydemir Y, Simkin A, Gascon E, Gao F-B. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol [Internet]. 2011/07/01. 2011;8(4):557–64. Available at: https://pubmed.ncbi.nlm.nih.gov/21697652
- Munoz JL, Rodriguez-Cruz V, Ramkissoon SH, Ligon KL, Greco SJ, Rameshwar P. Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level. Oncotarget. Ocak 2015;6(2):1190–201.
- Munoz JL, Rodriguez-Cruz V, Rameshwar P. High expression of miR-9 in CD133+ glioblastoma cells in chemoresistance to temozolomide. J cancer stem cell Res [Internet]. 2015;3:e1003. Available at: https://europepmc.org/articles/PMC4917210
Yıl 2024,
, 595 - 602, 09.12.2024
Öz
Aim: microRNAs (miRNAs) play a pivotal role in gene regulation, influencing various cellular processes such as differentiation, proliferation, and apoptosis. This study investigated the expression of three specific miRNAs (Hsa-miR-21-5p, Hsa-miR-9-5p, and Hsa-miR-200a-5p) in malign melanoma stem cells (CSCs) and non-stem cells (NSCs).
Method: CSCs and NCSCs were sorted from CHL-1 cells based on CD133 marker, a malignant melanoma cell line. CD133+ cells were treated with Hif1a, KLF4, and SHH siRNA and the expression levels of three different miRNAs were compared between groups.
Results: Our results revealed that Hsa-miR-200a-5p expression was similar in both cell groups. Conversely, Hsa-miR-21-5p and Hsa-miR-9-5p were significantly upregulated in NCSCs. Further analysis showed that the knockdown of KLF4 did not significantly affect the expression levels of these miRNAs. However, silencing SHH resulted in a substantial downregulation of Hsa-miR-21-5p and a significant upregulation of Hsa-miR-9-5p. Additionally, Hif1a knockdown led to the downregulation of both Hsa-miR-21-5p and hsa-miR-9-5p.
Conclusion: These findings highlight the complex regulatory mechanisms of miRNA expression in different cellular contexts and suggest potential roles for these miRNAs in response to specific gene silencing.
Anahtar Kelimeler
Destekleyen Kurum
Scientific Research Projects Coordination Unit at Ege University
Proje Numarası
20785
Teşekkür
The authors thank to the Scientific Research Projects Coordination Unit at Ege University for their financial support.
Kaynakça
- Moran B, Silva R, Perry AS, Gallagher WM. Epigenetics of malignant melanoma. Semin Cancer Biol [Internet]. 2018;51:80–8. Available at: https://www.sciencedirect.com/science/article/pii/S1044579X1730130X
- Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D. Epidemiological trends in skin cancer. Dermatol Pract Concept [Internet]. 30 Nisan 2017;7(2):1–6. Available at: https://pubmed.ncbi.nlm.nih.gov/28515985
- Hessler M, Jalilian E, Xu Q, Reddy S, Horton L, Elkin K, vd. Melanoma biomarkers and their potential application for in vivo diagnostic imaging modalities. Int J Mol Sci. 2020;21(24):9583.
- Liu Z, Wang H, Sun C, He Y, Xia T, Wang J, vd. ZWZ-3, a Fluorescent Probe Targeting Mitochondria for Melanoma Imaging and Therapy [Internet]. C. 13, Frontiers in Pharmacology . 2022. Available at: https://www.frontiersin.org/article/10.3389/fphar.2022.829684
- Kuşoğlu A, Biray Avcı Ç. Cancer stem cells: A brief review of the current status. Gene [Internet]. 2019;681:80–5. Available at: https://www.sciencedirect.com/science/article/pii/S0378111918310163
- Jain P, Pillai M, Duddu AS, Somarelli JA, Goyal Y, Jolly MK. Dynamical hallmarks of cancer: Phenotypic switching in melanoma and epithelial-mesenchymal plasticity. Semin Cancer Biol [Internet]. 2023;96:48–63. Available at: https://www.sciencedirect.com/science/article/pii/S1044579X23001293
- Boudreault J, Wang N, Ghozlan M, Lebrun J-J. Transforming Growth Factor-β/Smad Signaling Inhibits Melanoma Cancer Stem Cell Self-Renewal, Tumor Formation and Metastasis. C. 16, Cancers. 2024.
- Wu J, Li W, Su J, Zheng J, Liang Y, Lin J, vd. Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells. Sci Rep [Internet]. 2024;14(1):12270. Available at: https://doi.org/10.1038/s41598-024-62913-3
- Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, vd. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther [Internet]. 2020;5(1):8. Available at: https://doi.org/10.1038/s41392-020-0110-5
- Bu P, Luo C, He Q, Yang P, Li X, Xu D. MicroRNA-9 inhibits the proliferation and migration of malignant melanoma cells via targeting sirituin 1. Exp Ther Med [Internet]. 2017/06/13. Ağustos 2017;14(2):931–8. Available at: https://pubmed.ncbi.nlm.nih.gov/28810544
- Bustos MA, Ono S, Marzese DM, Oyama T, Iida Y, Cheung G, vd. MiR-200a Regulates CDK4/6 Inhibitor Effect by Targeting CDK6 in Metastatic Melanoma. J Invest Dermatol [Internet]. 2017;137(9):1955–64. Available at: http://www.sciencedirect.com/science/article/pii/S0022202X17315282
- Liu S, Kumar SM, Lu H, Liu A, Yang R, Pushparajan A, vd. MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma. J Pathol. Ocak 2012;226(1):61–72.
- Melnik BC. MiR-21: an environmental driver of malignant melanoma? J Transl Med [Internet]. 27 Haziran 2015;13:202. Available at: https://pubmed.ncbi.nlm.nih.gov/26116372
- Satzger I, Mattern A, Kuettler U, Weinspach D, Niebuhr M, Kapp A, vd. microRNA-21 is upregulated in malignant melanoma and influences apoptosis of melanocytic cells. Exp Dermatol. Temmuz 2012;21(7):509–14.
- van Kempen LC, van den Hurk K, Lazar V, Michiels S, Winnepenninckx V, Stas M, vd. Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression. Virchows Arch. Ekim 2012;461(4):441–8.
- Gajos-Michniewicz A, Czyz M. Role of miRNAs in Melanoma Metastasis. Cancers (Basel). Mart 2019;11(3).
- Rhim J, Baek W, Seo Y, Kim JH. From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells. Eylül 2022;11(18).
- Yang CH, Yue J, Pfeffer SR, Handorf CR, Pfeffer LM. MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells. J Biol Chem. Kasım 2011;286(45):39172–8.
- Xu D, Chen X, He Q, Luo C. MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1. Onco Targets Ther. 2016;9:7047–57.
- Park S-M, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. Nisan 2008;22(7):894–907.
- Klicka K, Grzywa TM, Mielniczuk A, Klinke A, Włodarski PK. The role of miR-200 family in the regulation of hallmarks of cancer. Front Oncol [Internet]. 2022;12. Available at: https://www.frontiersin.org/articles/10.3389/fonc.2022.965231
- Chen W-Y, Xu Y-Y, Zhang X-Y. Targeting GOLM1 by microRNA-200a in melanoma suppresses cell proliferation, invasion and migration via regulating PI3K/Akt signaling pathway and epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci. Ağustos 2019;23(16):6997–7007.
- Botti G, Cerrone M, Scognamiglio G, Anniciello A, Ascierto PA, Cantile M. Microenvironment and tumor progression of melanoma: new therapeutic prospectives. J Immunotoxicol. 2013;10(3):235–52.
- Yue B. Biology of the extracellular matrix: an overview. J Glaucoma. 2014;23(8 Suppl 1):S20-3.
- Ozdil B, Biray Avci C, Calik-Kocaturk D, Gorgulu V, Uysal A, Guler G, vd. Modulating cancer stem cell characteristics in CD133+ melanoma cells through HIF1α, KLF4, and SHH silencing Berrin. unpublished. 2024.
- Ozdil Bay B. MALİGN MELANOMA KANSER KÖK HÜCRE MODELİNDE HİF1A GENİNİN SUSTURULMASI İLE İNCELENMESİ Doktora Tezi HİF1A GENİNİN SUSTURULMASI İLE. 2023.
- Gunel NS, Birden N, Kurt CC, Bagca BG, Shademan B, Sogutlu F, vd. Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer. Mol Biol Rep [Internet]. 2021;48(8):6085–91. Available at: https://doi.org/10.1007/s11033-021-06616-2
- Metsalu T, Vilo J. ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic Acids Res [Internet]. 01 Temmuz 2015;43(W1):W566–70. Available at: https://doi.org/10.1093/nar/gkv468
- Varrone F, Caputo E. The miRNAs Role in Melanoma and in Its Resistance to Therapy. C. 21, International Journal of Molecular Sciences. 2020.
- Poniewierska-Baran A, Zadroga Ł, Danilyan E, Małkowska P, Niedźwiedzka-Rystwej P, Pawlik A. MicroRNA as a Diagnostic Tool, Therapeutic Target and Potential Biomarker in Cutaneous Malignant Melanoma Detection-Narrative Review. Int J Mol Sci. Mart 2023;24(6).
- Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev cancer. 2006;6(4):259–69.
- Ghafouri-Fard S, Gholipour M, Taheri M. MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets. Front Oncol [Internet]. 2021;11. Available at: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.608987
- Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. Şubat 2008;21(1):39–55.
- Madjd Z, Erfani E, Gheytanchi E, Moradi-Lakeh M, Shariftabrizi A, Asadi-Lari M. Expression of CD133 Cancer Stem Cell Marker in Melanoma: A Systematic Review and Meta-Analysis. Int J Biol Markers [Internet]. 01 Nisan 2016;31(2):118–25. Available at: https://doi.org/10.5301/jbm.5000209
- He Z, He J, Xie K. KLF4 transcription factor in tumorigenesis. Cell Death Discov [Internet]. 2023;9(1):118. Available at: https://doi.org/10.1038/s41420-023-01416-y
- Luo X, Zhang Y, Meng Y, Ji M, Wang Y. Prognostic significance of KLF4 in solid tumours: an updated meta-analysis. BMC Cancer [Internet]. 2022;22(1):181. Available at: https://doi.org/10.1186/s12885-022-09198-9
- Chen B, Li L, Li M, Wang X. HIF1A expression correlates with increased tumor immune and stromal signatures and aggressive phenotypes in human cancers. Cell Oncol (Dordrecht, Netherlands). Ekim 2020;43(5):877–88.
- Xu L, Li K, Li J, Liu L, Xu F, Xu Y, vd. MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance. Oncol (Tech Sci Press. 2022;24(3).
- Yuva-Aydemir Y, Simkin A, Gascon E, Gao F-B. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol [Internet]. 2011/07/01. 2011;8(4):557–64. Available at: https://pubmed.ncbi.nlm.nih.gov/21697652
- Munoz JL, Rodriguez-Cruz V, Ramkissoon SH, Ligon KL, Greco SJ, Rameshwar P. Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level. Oncotarget. Ocak 2015;6(2):1190–201.
- Munoz JL, Rodriguez-Cruz V, Rameshwar P. High expression of miR-9 in CD133+ glioblastoma cells in chemoresistance to temozolomide. J cancer stem cell Res [Internet]. 2015;3:e1003. Available at: https://europepmc.org/articles/PMC4917210
Toplam 41 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Kanser Hücre Biyolojisi, Moleküler Hedefler |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | 20785 |
| Yayımlanma Tarihi | 9 Aralık 2024 |
| Gönderilme Tarihi | 6 Ağustos 2024 |
| Kabul Tarihi | 11 Eylül 2024 |
| Yayımlandığı Sayı | Yıl 2024 |